Red blood cells are life-giving—as long as they stay confined to the insides of blood vessels. When there’s internal bleeding, on the other hand, erythrocytes can be life-threatening, especially for patients with a ruptured aneurysm or other source of bleeding in the brain.

It’s a problem that has kept Johns Hopkins neurosurgeon Rafael Tamargo as busy in the lab as in the operating room. Tamargo is studying ways to prevent the narrowing of brain blood vessels that occurs in more than 50 percent of patients in the days after a brain hemorrhage. About half of those patients with vasospasms suffer a stroke. Most researchers thought the culprit was the muscles in the artery walls, but in fact, says Tamargo, “the problem is inflammation.”

When red blood cells spill into tissue, the hemoglobin they carry is immediately grabbed by the protein haptoglobin. The combined molecule signals immune system cells to attack the now-toxic erythrocytes and whisk their remnants away through lymphatic vessels, the inflammatory process that causes swelling and bruising. But because the brain has no lymphatic vessels, immune system cells that respond to cerebral hemorrhaging linger, die and break down, releasing molecules that cause the brain’s blood vessels to narrow. In some patients, that triggers vasospasm and stroke.

But why in some patients and not others? Tamargo was among those who suspected the culprit was a second, more inflammatory version of haptoglobin that only some people carry. Studies have shown that mice carrying this type-2 haptoglobin suffer strokes after brain bleeding, while those without it don’t. “At first,” says Tamargo, “people were skeptical when I and others said it was the haptoglobin. Now it’s a hot idea.”

Tamargo is working to identify drugs that can counter the inflammatory response and the narrowing of blood vessels following cerebral hemorrhage. He’s currently focusing on nitric oxide, a neurotransmitter that, among other things, dilates blood vessels. “If we can find a drug that stimulates the body to produce more nitric oxide,” he says, “it might prevent vasospams.”

And that would give patients who’ve had a cerebral hemorrhage one less thing to worry about.

Challenge: Post-bleeding spasms in brain blood vessels that can lead to strokes

Approach: Counter inflammation from the protein that cleans up hemoglobin